Programming the lymph node microenvironment to enhance anti-tumor T cell immunity in neuroblastoma

Background and hypothesis Current cancer therapies rely on nonspecific chemotherapies which cause severe side effects without combating relapse. Therapeutic cancer vaccines aim to harness the adaptive immune response to specifically target and eliminate established tumors, while generating durable tumorspecific T cell responses to prevent relapse. Toll like receptor agonists (TLRas) such as CpG strongly activate dendritic cells (DCs) and show promise as adjuvants for cancer vaccines when co-administered with tumor associated antigens (TAAs). Current strategies are exploring direct vaccination with TLRas and TAAs to prime DCs in vivo, but are hampered by the instability of vaccine components, inefficient co-localization of antigen and adjuvant, and poor trafficking and persistence in lymph nodes (LN) tissues that orchestrate adaptive immunity. Direct LN injection of soluble vaccines show enhanced efficacy over systemic administration, but are limited by rapid flushing of vaccine components. Biomaterials offer the potential to enhance cancer vaccination by allowing sustained release, co-delivery, and protection of encapsulated cargo. We recently demonstrated that local delivery of non-toxic, degradable biomaterials loaded with antigens or adjuvants potently enhances antigen specific T cell immunity. Building on this work, we hypothesized that local introduction of particles loaded with CpG and soluble tumor lysates (TLs) might combat tumor progression in murine neuroblastoma models.